N-tert-butoxycarbonyl-3-methoxy-2-methylaniline → 1-[2-(Tert-butoxycarbonylamino)-6-methoxyphenyl]-2-butanone

HRID 49452

Reaction equation

C([Li])(CC)C.[C:6]([O:10][C:11]([NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[C:15]=1[CH3:22])=[O:12])([CH3:9])([CH3:8])[CH3:7].CON(C)[C:26](=[O:29])[CH2:27][CH3:28]>C1CCCCC1.C1COCC1>[C:6]([O:10][C:11]([NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[C:15]=1[CH2:22][C:26](=[O:29])[CH2:27][CH3:28])=[O:12])([CH3:9])([CH3:8])[CH3:7]

Participants

Conditions

Temperature: -60 °C

Procedure

A solution of 140 mL (0.18 mol) of 1.3M sec-butyl lithium in cyclohexane was added slowly to N-tert-butoxycarbonyl-3-methoxy-2-methylaniline (21.3 g, 0.09 mol) in 250 mL of THF keeping the temperature below −40° C. with a dry ice-ethanol bath. The bath was removed and the temperature allowed to rise to 0° C. and then the bath replaced. After the temperature had cooled to −60° C., 18.5 g (0.18 mol) of N-methoxy-N-methylpropanamide in an equal volume of THF was added dropwise. The reaction mixture was stirred 5 minutes, the cooling bath removed and stirred an additional 18 hours. It was then poured into a mixture of 300 mL of ether and 400 mL of 0.5N HCl. The organic layer was separated, washed with water, brine, dried over MgSO4, and concentrated at reduced pressure to give 25.5 g of a crude of 1-[2-(tert-butoxycarbonylamino)-6-methoxyphenyl]-2-butanone. This material was dissolved in 250 mL of methylene chloride and 50 mL of trifluoroacetic acid and stirred for a total of 17 hours. The mixture was concentrated at reduced pressure and ethyl acetate and water added to the remaining oil. The ethyl acetate was separated, washed with brine, dried (MgSO4) and concentrated. The residue was chromatographed three times on silica eluting with 20% EtOAc/hexane to give 13.9 g of 2-ethyl-4-methoxy-1H-indole.

Workup

customThe bath was removed
customto rise to 0° C.
customthe cooling bath removed
stirringstirred an additional 18 hours
additionIt was then poured into a mixture of 300 mL of ether and 400 mL of 0.5N HCl
customThe organic layer was separated
washwashed with water, brine
dry with materialdried over MgSO4
concentrationconcentrated at reduced pressure

Sources & evidence

ORD record: ord-98a0b0d047db4f92872735d7295efbf8
Source dataset: uspto-grants-2004_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06706752B1

Linked notes

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